Dynamics of single cell property distributions in Chinese hamster ovary cell cultures monitored and controlled with automated flow cytometry

James Kacmar, Friedrich Srienc

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Two important variables that are often not measured online in Chinese hamster ovary (CHO) cell cultures are cell number concentration and culture viability. We have developed an automated flow cytometry system that measured the cell number concentration, single cell viability based on propidium iodide (PI) exclusion, and single cell light scattering from bioreactor samples every 30 min. The bioreactor was monitored during batch growth, and then the cell number concentration was controlled at a set point during cytostat operation. NH4Cl was added during steady state operation in cytostat mode to monitor the transient cell population response to adverse growth conditions. The automated measurements correlated well to cell concentration and viability determined manually using a hemacytometer. The described system provides a method to study mammalian cell culture physiology and dynamics in great detail. It presents a new method for the monitoring and control of animal cell culture.

Original languageEnglish (US)
Pages (from-to)410-420
Number of pages11
JournalJournal of Biotechnology
Volume120
Issue number4
DOIs
StatePublished - Dec 6 2005

Bibliographical note

Funding Information:
We thank the National Science Foundation for supporting this work (BES 0109383). J. Kacmar was a recipient of a NIH training grant fellowship in biotechnology.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • Automated flow cytometry
  • Bioreactor control
  • Bioreactor monitoring
  • Cytostat
  • Mammalian cell culture
  • Single cell heterogeneity

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